RESEARCH DESIGN AND METHODS

The studies were approved by the TNO Nutrition and Food Research Medical Ethics Committee, and all participants gave informed
consent. The trials were originally designed to study the effects of coffee and caffeine on plasma concentrations of homocysteine,
and the study designs have been reported in detail previously (17,18). Participants were regular coffee consumers (more than
five cups/day) and did not have known diabetes.

The first study was a 4-week crossover study that compared the effects of regular paper-filtered coffee consumption with that
of coffee abstinence. A total of 40 volunteers used 1 l of coffee (70 g coffee grounds) for 4 weeks and abstained from coffee
for 4 weeks in random order. Fourteen participants did not complete the trial because of nausea and restlessness (n = …